1-Nitroso-1,2,3,4-tetrahydroquinoline and 1-nitroso-indoline compounds

ABSTRACT

This invention relates to N-nitroso compounds having the formula ##STR1## wherein R and R&#39; each are selected from hydrogen and alkyl, Z is --CN or --COOR&#34; wherein R&#34; is alkyl and n is a positive integer from 1 to 7. These compounds are useful as intermediates in the preparation of photographic silver halide developing agents.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application is a continuation-in-part of copending U.S. patentapplication Ser. No. 592,397 filed July 2, 1975, now abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to novel N-heterocyclic compounds possessing anitroso group on the heterocyclic N atom, which compounds are useful asintermediates in the preparation of photographic silver halidedeveloping agents.

2. Description of the Prior Art

In recent years, there has been a growing interest in heterocyclicphotographic developing agents, i.e., developers containing aheterocyclic ring as part of their structure. Some of these developingagents have the conventional hydroxyl or amino developing groupssubstituted on adjacent carbon atoms of a heterocyclic ring to providestructures similar to those of the developing agents in the aliphaticand aromatic series. Still other heterocyclic developing agents have oneof the functional developing groups included as part of the heterocyclicring. Copending U.S. patent application Ser. No. 721,859 of Stanley M.Bloom, which is a continuation-in-part of application Ser. No. 592,398filed July 2, 1975, now abandoned, which, in turn, is acontinuation-in-part of application Ser. No. 451,740 filed Mar. 18,1974, now abandoned, discloses and claims the use of certain tricyclicdeveloping agents of the latter type, i.e., developing agents having oneof the functional developing groups included as part of a heterocyclicring.

N-nitrosos compounds useful as intermediates in the synthesis of theaforementioned tricyclic developing agents comprise the subject matterof the present invention.

SUMMARY OF THE INVENTION

It is the primary object of the present invention to provide certainN-heterocyclic compounds possessing a nitroso group on the heterocyclicN atom.

It is another object of the present invention to provide heterocycliccompounds useful as intermediates in the preparation of photographicdeveloping agents.

Other objects of this invention will in part be obvious and will in partappear hereinafter.

The invention accordingly comprises the products and compositionspossessing the features, properties and the relation of elements whichare exemplified in the following detailed disclosure, and the scope ofthe application of which will be indicated in the claims.

For a fuller understanding of the nature and objects of the invention,reference should be had to the following detailed description.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Specifically, the compounds provided by the present invention may berepresented by the formula ##STR2## wherein R and R' each are hydrogenor lower alkyl having 1 to 4 carbon atoms, Z is --CN or --COOR" whereinR" is alkyl, usually lower alkyl having 1 to 4 carbon atoms and n is apositive integer from 1 to 7.

In a preferred embodiment, n is 1 or 2 and the subject compounds areN-nitroso derivatives of indolines or 1,2,3,4-tetrahydroquinolines. Thepreferred compounds may be represented by the formula ##STR3## whereinR, R' and Z have the same meaning given in formula I above and n is 1 or2.

Specific examples of preferred N-nitroso compounds within the scope ofthe present invention are as follows: ##STR4##

The subject compounds may be synthesized by nitrosation of a compoundhaving the formula ##STR5## wherein R, R', n and Z have the same meaninggiven in formula I above. Usually, the nitrosation is carried out byadding an aqueous solution of sodium nitrite to a solution of theselected starting compound in dilute aqueous hydrochloric acid at roomtemperature and then isolating the corresponding N-nitroso compound fromthe reaction solution. Despite the bulky substituent in the 2-positionof the starting compound, it has been found that nitrosation isefficient giving the N-nitroso compound as the major product in allcases.

The acid ester and the nitrile starting materials may be prepared in aconventional manner. For example, acid esters, such as, ethyl1,2,3,4-tetrahydro-2-quinolylacetate and nitriles, such as,1,2,3,4-tetrahydro-2-quinolylacetonitrile are known and may besynthesized according to the procedures reported by G. Jones and J.Wood, Tetrahedron, Vol. 21, pp. 2951-2971 (1965). The indoline estersand nitriles may be prepared, for example, by reduction of thecorresponding indoles.

The following examples illustrate the preparation of compounds withinthe scope of the invention and are given for purposes of illustrationonly.

EXAMPLE 1 Preparation of ##STR6##

A colorless solution of 16 gms. of ethyl1,2,3,4-tetrahydro-2-quinolylacetate in 150 mls. of 10% hydrochloricacid was stirred at room temperature, and 5 gms. of sodium nitrite in 30mls. of water were added dropwise over a period of about 20 minutes. Noheat was evolved. After addition was complete, stirring was continuedfor another 20 minutes. The solution turned orange, and a dark orangeoil precipitated. The orange oil was taken up in benzene, and thebenzene solution was washed to neutral, dried and stripped. The darkorange oil was then taken up in hexane, and after boiling, the solutionwas decanted from the brown insoluble residue. The hexane solution wasthen cooled in an ice bath and decanted from the yellow-brown oil thatformed. The decanted solution was stripped to give the title compound asa yellow oil, 14 gms., ν_(max) 1440 cm⁻¹.

EXAMPLE 2 Preparation of ##STR7##

The procedure of Example 1 was repeated using as the acid ester startingmaterial, the compound ##STR8## (1.3 gms) in 15 mls. of 15% hydrochloricacid and 1 gm. of sodium nitrite in 5 mls. of water to give thecorresponding N-nitroso intermediate as a yellow oil, ν_(max) 1460 cm⁻¹.

EXAMPLE 3 Preparation of ##STR9##

A solution of 9.7 gms. of 1,2,3,4-tetrahydro-2-quinolylacetonitrile in200 mls. of 10% hydrochloric acid was stirred at room temperature, and 5gms. of sodium nitrite in 25 mls. of water were added slowly. Theresulting solution became a reddish color and then a red-brown oilprecipitated. The solution was allowed to stand for about 4 days. Thered-brown oil was extracted into benzene, and the benzene solutionwashed and dried and then stripped to leave about 8 gms. of brown oil.The aqueous reaction solution was made basic and again extracted withbenzene to give an additional gram of brown oil. The oils were combinedand chromatographed on Florisil using benzene as the eluent. The titlecompound was collected as an oil, 3 gms., ν_(max) 1440 cm⁻¹.

EXAMPLE 4 Preparation of ##STR10##

To a 3.3 gm sample (0.016M) of ethyl-2-indolinylacetate was added 40 cc.of 10% hydrochloric acid and the mixture cooled to 10°-20° C. A solutionof 3.5 gms of sodium nitrite (0.05M) in 20 cc. of water was addeddropwise. Then the mixture was allowed to stir at 10°-20° C. for 1 hour.

The product was extracted into benzene and the benzene layer washed witha little sodium bicarbonate solution. After drying, over sodium sulfate,the benzene solution was filtered and the solvent evaporated on a rotaryevaporator. The title compound was obtained as a brown oily solid.

The ethyl-2-indolinylacetate used in the above example was prepared asfollows:

a. 22.2 gm (0.17M) of ethylacetoacetate was added dropwise to awell-stirred suspension of 7.6 gm (0.18M) of sodium hydride, (57% inmineral oil) in 300 ml of dry benzene, keeping the mixture in a nitrogenatmosphere. The reaction mixture was stirred for 1 hour under nitrogen.33.9 gm of o-nitrophenylacetylchloride in 100 cc. dry benzene was addeddropwise over a period of approximately 45 minutes. The mixture wasallowed to stir for 1 hour at room temperature. The mixture was thendiluted with 150 cc. dry benzene and washed twice with 150 cc. water.The benzene layer was dried over anhydrous sodium sulfate. (Additionalproduct can be obtained by acidfying the water layer and extracting withethyl ether). The solvent was removed and theethyl-o-nitrophenylacetylacetoacetate product was crystallized bytreatment with methanol and recovered as a pale colored material.

b. 30 gm (0.103M) ethyl-o-nitrophenylacetylacetoacetate was added over aperiod of 15-20 minutes to a saturated ammoniacal ethanol solution(prepared by bubbling NH₃ gas into 400 cc. absolute for 15-20 minuteswhile cooling the solution to 0°-5° C.). The orangy mixture was stirredfor 1 hour at 5°-10° C. and then left in the refrigerator overnight. Theethyl-γ-2-nitrophenylacetoacetate crystals formed were filtered anddried in vacuum. Additional solid was obtained after evaporation of thefiltrate and washing with water to remove any amide formed.

c. A sample of 12.0 gm (0.048M) of ethyl-γ-2-nitrophenylacetoacetate wasdissolved in 200 cc. glacial acetic acid. Approximately 21/2 spatulas of5% Pd/C was added to the solution and the compound was reduced on theParr hydrogenator. Ethyl-2-indolylacetate was obtained as a dark orangyoily liquid after removal of catalyst and solvent.

d. 8.8 gm (0.04M) of the indole prepared in step (c) was dissolved in150 cc. glacial acetic acid and cooled to .sup.± 20° C. in an ice bath.2.4 gm of sodium cyanoborohydride was added slowly over a period of10-15 minutes. The mixture was allowed to stir at 20° C. for 1 hour andthen poured into 150 cc. ice water. The product was extracted with ethylether and dried over anhydrous sodium sulfate. The ethyl ether wasremoved leaving ethyl-2-indolinylacetate as a dark oily material whichwas purified by extraction in petroleum ether/methanol and saltsolution.

As noted previously, the N-nitroso compounds of the subject inventionare useful as intermediates in the synthesis of photographic developingagents. It has been found that these compounds undergo ring-closure toyield developing agents of the formula: ##STR11## wherein Y is ═O or ═NHand R, R' and n have the same meaning given formula I above.

Depending upon the particular nitroso compound, ring-closing to thedeveloping agent product may be achieved by reduction alone or byreduction followed by cyclization. For example, ring-closing of theN-nitroso quinoline compounds may be carried out by treating theN-nitroso compounds with zinc dust in a solvent, such as dilute glacialacetic acid, while maintaining the temperature between about 10° and 20°C. The reaction mixture is then stirred at room temperature, the zincdust removed by filtration and the developing agent product isolatedfrom the filtrate. Ring-closing of the N-nitroso indoline compounds maybe carried out by electrolytic reduction followed by heating inquinoline. As an illustration, developing agents were prepared from theN-nitroso compounds of Examples 1 to 4 as follows:

COMPOUND A Preparation of ##STR12##

Ethyl 1-nitroso-1,2,3,4-tetrahydro-2-quinolylacetate obtained in Ex. 1(14 gms.) was dissolved in dilute acetic acid (60 mls. water:80 mls.glacial acetic acid). The resulting solution was stirred at 16° C. in anice bath under nitrogen, and 5 gms. of zinc dust were added in threeportions. After the first addition, the temperature rose to 20° C. andthe mixture was stirred in the ice bath for about 20 minutes until thetemperature was about 16° C. The second portion was added, and thetemperature rose to about 18° C. after which stirring in the ice bathwas continued for another 15 minutes. After the third addition, thetemperature rose from 13° to 17° C. The mixture was then removed fromthe ice bath and stirred at room temperature for about 30 minutes atwhich time the temperature was about 25° C.

The zinc was removed from the mixture by filtering through a sinteredfunnel. The filtrate was stripped at 55° C. leaving a gummy crystallineresidue that was refrigerated overnight. The residue was taken up inchloroform/water, and the solvent was washed well, dried and stripped at38° C. leaving a yellow oil (13.5 gms.). The oil was taken up in amixture of hexane and benzene and the title compound was recovered aswhite crystals from the solvent mixture by filtering and drying invacuuo over P₂ O₅ at room temperature melting range 196°-197° C.

COMPOUND B Preparation of ##STR13##

The nitroso compound prepared in Ex. 2 (1 gm) was dissolved in diluteacetic acid (8 mls. water: 11 mls. glacial acetic acid) in a water bathat a temperature of about 22° C. Zinc dust (1 gm) was added in portionsto maintain the temperature at about 31°-32° C. After the addition wascomplete, the reaction mixture was heated at about 55° C. for 1 hour andthen at 75° C. for about one-half hour. The reaction mixture was cooled,filtered to remove the zinc and stripped leaving a gummy solid. Thesolid was taken up in chloroform/water, and the solvent layer washed toneutral, dried and stripped to a brown oil. Crystallization of the oilfrom hexane/benzene gave a brown flocculant solid which was removed byfiltration. Upon cooling and scratching, off-white crystals formed inthe filtrate which were collected by filtration and chromatographed onsilica gel using benzene, benzene/5% ether, benzene/10% ether andbenzene/25% ether. The oil eluted with benzene/10% ether crystallizedand the solid obtained was recrystallized to give the title compound asoff-white crystals (melting range 148°-150° C.).

COMPOUND C Preparation of ##STR14##

1-nitroso-1,2,3,4-tetrahydro-2-quinolylacetonitrile obtained in Ex. 3 (3gms.) was dissolved in 20 mls. of glacial acetic acid and this solutionadded dropwise to a mixture of zinc dust in 20 mls. of water cooled to15° C. and stirred under nitrogen. Addition was conducted at a rate tokeep the temperature at about 15°-16° C. and the nitrile solution washedin with 5 mls. of glacial acetic acid. The reaction mixture was stirredin an ice bath for about one-half hour and then allowed to come to roomtemperature.

The zinc was removed by filtering through a sintered funnel undernitrogen. The filtrate was stripped under vacuum at about 40° C. toleave a solid that was taken up in chloroform/water under nitrogen. Thewater layer was pink--then blue--then colorless. The solvent layer wasdried and stripped leaving a gummy white crystalline solid. A mixture ofchloroform/benzene/hexane was added to the white crystalline solid and agray solid crystallized which was dried in vacuo at room temperature.The gray solid was dissolved in benzene and the benzene solutionfiltered through a sintered funnel to remove remaining zinc. Shiny whiteplates slowly crystallized in the filtrate upon standing. The whileplates were dried under vacuum at room temperature to give 1.0 ± gms. ofthe title compound (melting range 152°-154° C.).

COMPOUND D Preparation of ##STR15##

1. Ethyl 2-(N-nitrosoindolinyl) acetate (0.015-0.025 mole) was dissolvedin 400 ml of a 50/50 mixture of 0.10M phosphate buffer and absoluteethanol. The dark solution was transferred to the cathode compartment ofa water-jacketed electrolysis cell. Phosphate-ethanol mixture (60 ml)and 4N hydrochloric acid (5 ml) were added to the anode compartment. Thesolution was degassed for 15 minutes with nitrogen followed by theadjustment of pH of the cathode compartment to approximately 4.0 with 4NHCl. The reduction occurred at a mercury cathode (constant potential,1.200 volts vs. saturated calomel electrode). A rotating platinumelectrode was used as the anode. Initially the current ranged from200-300 ma and after about 15-20 hours had decreased to 15 -20 ma. Thereduction of substrate was monitored by polarographic analysis and adigital coulometer, the latter revealing a four electron process. Inconcluding the electrolysis the light yellow solution was transferredfrom the electrolysis cell, and the ethanol was evaporated. The aqueousmixture was extracted with chloroform, dried over anhydrous MgSO₄ andevaporated to give the hydrazine as a dark oil in 90-95% yield. The freebase was converted to the hydrochloride salt with absolute ethanolsaturated with HCl gas at 0° C. The salt was filtered and recrystallizedfrom ethanol-ether to give a pale yellow solid, (m.p. 153°-155°).Reaction of the hydrazine salt with acetone give the correspondingSchiff base, m.p. 157°-158°.

2. The reduced compound (0.656 mmole) in CDCl₃ was placed in apear-shaped flask and the CDCl₃ removed in vacuo. Quinoline(redistilled; 12.692 mmole) and a micro-stirrer bar were added and airremoved by blowing a stream of nitrogen over the mixture for some time.Meanwhile an oil bath was preheated to 190°-195° C. Then the mixture wasplaced in the bath, stirred under nitrogen at 187°-195° C. (mostlyaround 193° C.) for 10 minutes, then removed and allowed to cool undernitrogen. As much quinoline as possible was distilled off in vacuo (bathtemperature approximately 90° C., 0.27 mm) and the residue keptovernight under nitrogen. The mixture was shaken with saturated aqueouspotassium bicarbonate to neutralize any hydrochlorides and thenextracted with chloroform (4 ml and 2 × 1 ml). The dried chloroformextracts were washed once with saturated aqueous potassium bicarbonate(about 4 ml), dried with magnesium sulfate and evaporated first in astream of nitrogen to remove chloroform and then in vacuo (bathtemperature about 90° C., 0.27 mm) to remove as much quinoline aspossible. The resulting dark brown gum comprising the title compound wastaken up in CDCl₃ (0.9 ml) freed from traces of magnesium sulfate andafter running a ¹³ C nmr spectrum which confirmed the presence of thetitle compound, the compound was recovered by evaporation in a stream ofnitrogen, mixing the partly crystallized residue with ether and thenremoving the ether (filter-stick). The treatment with ether was repeatedthree times to remove as much quinoline as possible. To the residue wasadded chloroform (about 1 ml) and the mixture cooled to -60° C. and thechloroform removed. To the residual crystals was added chloroform, themixture cooled again and the operation repeated. The crystalline residue(somewhat discolored prisms) was dried in vacuo leaving the titlecompound having a melting range of 150°-153.5° C.

To illustrate its usefulness as a reducing agent for silver halide, afew crystals of the title compound were placed on Velox paper (aphotographic printing paper containing a silver chloride emulsion), anda few drops of 1N aqueous sodium hydroxide was placed on the crystals todissolve them. The silver salt in the area of the dissolved crystals wasreduced as evidenced by the appearance of a dark spot. No darkeningoccurred with the 1N sodium hydroxide alone.

To illustrate the usefulness of the ring-closed compounds inphotography, Compound A was employed as a silver halide developing agentas follows:

A Polaroid Land Type 105 negative comprising a photosensitive silverhalide emulsion was exposed in an automatic recording densitometer andprocessed by spreading a layer of processing composition approximately0.0016 inch thick between the exposed emulsion and a superposed PolaroidLand Type 107 image-receiving element. The processing compositionemployed was prepared by adding 0.35 gm. of Compound A to 10 cc. of thefollowing formulation:

    ______________________________________                                        Water                     40 cc.                                              Potassium Hydroxide                                                           (Aqueous 45% w/w solution 6.6 gm.                                             Potassium thiosulfate     1.0 gm.                                             Sodium carboxymethyl cellulose                                                                          2.0 gm.                                             ______________________________________                                    

After an imbibition time of approximately 1 minute, the negative wasstripped from the image-receiving element. The maximum and minimumreflection densities measured for the positive image were 1.0 and 0.12,respectively.

In a comparative example, the above procedure was repeated except that amolecular equivalent (0.3 gm./10 cc.) of 1-phenyl-3-pyrazolidone("Phenidone"), a conventional developing agent was used instead ofCompound A. The positive image obtained showed substantially lessdensity as evidenced by maximum and minimum reflection densities of 0.4and 0.03, respectively.

Since certain changes may be made in the above compositions andprocesses without departing from the scope of the invention hereininvolved, it is intended that all matter contained in the abovedescription should be interpreted as illustrative and not in a limitingsense.

What is claimed is:
 1. A compound of the formula ##STR16##wherein R andR' each are hydrogen or lower alkyl having 1 to 4 carbon atoms, n is apositive integer 1 or 2 and Z is --CN or --COOR" wherein R" is loweralkyl having 1 to 4 carbon atoms.
 2. A compound as defined in claim 1wherein n is
 1. 3. A compound of the formula ##STR17##wherein R and R'each are hydrogen or lower alkyl having 1 to 4 carbon atoms and Z is--CN or --COOR" wherein R" is lower alkyl having 1 to 4 carbon atoms. 4.A compound as defined in claim 3 wherein R and R' are hydrogen.
 5. Acompound as defined in claim 3 wherein R and R' each are alkyl.
 6. Acomposition as defined in claim 3 wherein Z is --CN.
 7. A compound asdefined in claim 3 wherein Z is --COOR".
 8. The compound ##STR18## 9.The compound
 10. The compound ##STR19##
 11. The compound